Trauma is a leading cause of morbidity and mortality in the United States as well as a source of substantial health care expenditures and lost productivity.1-4 Multiple organ failure (MOF) is common among the most seriously-injured and is the leading cause of morbidity and mortality among those who survive the immediate post-injury period.5 In addition, patients who develop MOF following trauma require extended intensive care and specialized healthcare resources.6-8 The ability to rapidly and accurately identify patients most likely to develop MOF early in the post-injury period would be extremely useful and would allow for more aggressive, targeted therapeutic strategies and focused resource allocation. Unfortunately, no criteria previously existed to identify on arrival to the hospital those patients most at risk for the development of MOF. We therefore recently derived and internally validated a multivariable instrument, the Denver Trauma Organ Failure (TOF) Score, for use in the emergency department (ED) to predict subsequent development of MOF in trauma patients. The first hypothesis is that when applied to a large, heterogeneous adult trauma population in the ED, the Denver TOF Score will accurately predict the development of MOF within seven days of hospitalization. The second hypothesis is that when applied to adult trauma patients in the ED, the Denver TOF Score will be more sensitive and specific for predicting the development of MOF within seven days of hospitalization than clinical judgment of emergency physicians. The third hypotheses are that in-hospital mortality and intensive care resource utilization (defined by need for and duration of mechanical ventilation, invasive procedures, length of intensive care and hospital stay, and total costs) will increase incrementally among adult trauma patients categorized into low- (Denver TOF Score 0-1), moderate- (Score 2-3), and high-risk (Score e4) groups, respectively. The Specific Aims therefore include: (1) performing a multi-center prospective cohort study using three institutions from the Western Emergency Services Translational Research Network (WESTRN) to externally validate the Denver TOF Score;(2) performing a multi-center prospective cohort study using the same three institutions to compare the Denver TOF Score to emergency physician judgment for identifying those who will develop MOF;and (3) performing a single-center retrospective cohort study to compare in-hospital mortality and intensive care resource utilization among patients categorized into low-, moderate-, and high-risk groups by the Denver TOF Score. PUBLIC HEALTH RELEVANCE: The proposed research will result in a valid and generalizable post-injury multiple organ failure (MOF) prediction instrument, the Denver Trauma Organ Failure (TOF) Score. Use of the Denver TOF Score may allow for: (1) selection of patients who require more aggressive, targeted resuscitation and monitoring;(2) improved resource allocation;and (3) improved secondary triage to identify patients who require care at designated tertiary-care trauma centers. Ultimately, use of this instrument may decrease the incidence of organ failure and reduce the morbidity, mortality, and economic burden associated with trauma.